| Literature DB >> 31123109 |
Emma K Persson1,2, Kenneth Verstraete3,4, Ines Heyndrickx1,2, Elien Gevaert5, Helena Aegerter1,2, Jean-Michel Percier6, Kim Deswarte1,2, Koen H G Verschueren3,4, Ann Dansercoer3,4, Delphine Gras7, Pascal Chanez7,8, Claus Bachert5,9, Amanda Gonçalves10,11, Hanne Van Gorp1,2, Hans De Haard6, Christophe Blanchetot6, Michael Saunders6, Hamida Hammad1,2, Savvas N Savvides12,4, Bart N Lambrecht13,2,14.
Abstract
Although spontaneous protein crystallization is a rare event in vivo, Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs derived from patients showed crystal packing and Gal10 structure identical to those of Gal10 crystals grown in vitro. When administered to the airways, crystalline Gal10 stimulated innate and adaptive immunity and acted as a type 2 adjuvant. By contrast, a soluble Gal10 mutein was inert. Antibodies directed against key epitopes of the CLC crystallization interface dissolved preexisting CLCs in patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E (IgE) synthesis, and bronchial hyperreactivity (BHR) in a humanized mouse model of asthma. Thus, protein crystals may promote hallmark features of asthma and are targetable by crystal-dissolving antibodies.Entities:
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Year: 2019 PMID： 31123109 DOI： 10.1126/science.aaw4295
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728